2024 Leading Research Achievements
We are pleased to present you with the 2024 Leading Research Achievements by BBRF Grantees, Prize Winners & Scientific Council Members. They are presented in the order of their publication in scientific journals.
Suicide Risk Fluctuates Across the Menstrual Cycle, Affecting Different Women Differently
Basic Research; Diagnostic Tools/Early Intervention: Suicide Prevention
- Tory Anne Eisenlohr-Moul, Ph.D., University of Illinois, Chicago; 2018 BBRF Young Investigator
The new research reveals how suicide risk fluctuates not only in correspondence with the menstrual cycle and shifting hormone levels, but also how symptoms fluctuate daily within individuals and how impacts vary from person to person. “While past suicide research has highlighted broad psychopathological and sociodemographic factors as predictors of suicide risk, our study reveals an acute peri-menstrual risk period for suicidal ideation and planning,” the team wrote. This, they said, “presents an opportunity for biological and psychosocial intervention.” Read more.
American Journal of Psychiatry, January 1, 2024
Preliminary Trial of Psychoactive Drug Ibogaine Yields ‘Initial Evidence’ for Powerful Therapeutic Potential
Next-Generation Therapies: PTSD, Depression, Anxiety
- Nolan R. Williams, M.D., Stanford University; 2024 BBRF Colvin Prize; 2019 BBRF Klerman Prize; 2018, 2016 BBRF Young Investigator
In a small, preliminary clinical test in military veterans, researchers obtained “initial evidence” suggesting the psychoactive compound ibogaine, when co-administered with magnesium to boost safety, “could be a powerful therapeutic” to safely treat a variety of psychiatric symptoms, including PTSD, depression, anxiety, and suicidality, which can emerge following traumatic brain injury. Read more.
Nature Medicine, January 5, 2024
In Childhood Anxiety, CBT Helps By Normalizing Hyperactive Brain Circuits, Study Finds
Basic Research: Anxiety
- Simone P. Haller, D. Phil, National Institute of Mental Health; 2020 BBRF Young Investigator
A study of brain network and circuit responses in young people with anxiety disorders who were treated with cognitive behavioral therapy (CBT) suggests how the therapy helps to normalize some (but not all) irregularities likely involved in generating anxiety symptoms. This in turn suggests how CBT and possible adjuncts to it might be modified to improve outcomes. Among the team’s findings: CBT may more effectively target cortical circuits, while subcortical dysfunction (including in limbic areas like the amygdala) may lag in responsivity and/or might require more direct interventions to alter exaggerated defensive reactions. Read more.
American Journal of Psychiatry, January 24, 2024
How Immune Activation May Alter the Brain and Cause Depression-Related Behavior During Chronic Social Stress
Basic Research: Depression
- Scott J. Russo, Ph.D., Icahn School of Medicine at Mount Sinai; BBRF Scientific Council; 2008, 2006 BBRF Young Investigator
- Flurin Cathomas, M.D., Mount Sinai / Psychiatric University Hospital Zurich; 2020 BBRF Young Investigator
This research indicates a specific mechanism through which stress and immune activation combine to alter behavior. A protein called MMP8, released during chronic social stress in mice by circulating immune cells, was able to invade the brain and alter the shape of the space between neurons. This can adversely affect the nucleus accumbens and possibly other brain areas. In mouse experiments, this mechanism was causally linked with social avoidance, an adverse behavioral change seen in human depression.” Read more.
Nature, February 7, 2024
A Food-Seeking Circuit in the Brain That Can Override Hunger or “Fullness” Signals May Shed Light on Eating Disorders
Basic Research: Eating Disorders
- Fernando M. C. V. Reis, Ph.D., University of California, Los Angeles; 2022, 2018 BBRF Young Investigator
- Avishek Adhikari, Ph.D., University of California, Los Angeles; 2014 BBRF Young Investigator
Researchers discovered that a specific group of neurons in a region of the brainstem (called the periaqueductal grey or PAG) previously associated with fear, when activated, induces mice to forage and eat even when they are not hungry—especially rewarding highly caloric foods. The research could provide important insights into eating disorders such as binge eating disorder and anorexia nervosa. Read more.
Nature Communications, March 7, 2024
A Stem Cell-Based Therapeutic ‘Rescue Strategy’ is Developed for Timothy Syndrome, an Autism Spectrum Disorder
Next-Generation Therapies: Autism Spectrum Disorders
- Sergiu P. Pasca, M.D., Stanford University; 2017 BBRF Independent Investigator; 2012 BBRF Young Investigator
Published experiments demonstrated a potential therapeutic “rescue strategy” using stem cell technology for the neurodevelopmental disorder Timothy Syndrome (TS), one of the autism spectrum disorders. By modifying messenger RNA activity for a gene involved in disease pathology, researchers prevented the emergence of disease pathology in human neurons implanted in living mice. Those neurons were generated with stem cell technology that Dr. Pasca and several other grantees have pioneered over the years— the technological predicate to this rapid translation to illness-relevant experiments. Read more.
Nature, April 24, 2024
New First-in-Class Schizophrenia Medicine Reduced Positive and Negative Symptoms in Decisive Phase 3 Trials
Next-Generation Therapies: Schizophrenia
- Steven M. Paul, M.D., Karuna Therapeutics; BBRF Scientific Council Emeritus
- Carol A. Tamminga, M.D., University of Texas (UT) Southwestern Medical School; BBRF Scientific Council; 2011 BBRF Lieber Prize; 2010, 1998 BBRF Distinguished Investigator
KarXT (xanomeline-trospium), a new medicine for treating schizophrenia— one that appears to help reduce both positive and negative symptoms of the illness—performed well in two phase 3 clinical trials reported in 2024 that contributed to the drug’s approval by the FDA in September (its trade name is Cobenfy). It is the first antipsychotic treatment that does not target the D2 dopamine receptor, targeting instead two muscarinic receptors called M1 and M4 with the aim of indirectly impacting the balance between the dopamine and acetylcholine systems, including in the brain’s striatum, which in turn might help therapeutically address pathology that gives rise to psychosis. Read more.
JAMA Psychiatry, May 1, 2024
The Lancet, January 13, 2024
Study of One Psychedelic Drug Suggests How It Might be Modified to Eliminate Psychedelic Effects While Retaining Therapeutic Ones
Basic Research; Next-Generation Therapies: PTSD, Anxiety, Depression
- Lyonna F. Parise, Ph.D., Icahn School of Medicine at Mount Sinai; 2022 BBRF Young Investigator
A detailed study of how the psychedelic drug 5-MeO-DMT interacts with receptors for the neurotransmitter serotonin has suggested that a modified version of the drug that targets the serotonin 1A receptor may not generate psychedelic effects while preserving some of the potential therapeutic effects attributed in various studies to psychedelics in depression, PTSD, and other illnesses. Read more.
Nature, May 8, 2024
Experiments Point to Possible Next-Gen Drug Therapies for Bipolar Disorder, Including for Lithium Non-Responders
Basic Research; Next-Generation Therapies: Bipolar Disorder
- Anouar Khayachi, Ph.D., McGill University; 2022 BBRF Young Investigator
Researchers used stem cell-based technology to study differences in cells sampled from bipolar disorder (BD) patients who respond to lithium vs. those who do not. This led to discovery of two ways to reduce hyperactivity in neurons, a characteristic problem in BD. The research suggests that activation of Akt, a signaling pathway, and AMPK, a protein complex, could be targets for next-gen therapeutics for BD. Personalized medicine for BD, if realized, could address the lag between diagnosis and therapy selection, and reduce the risk of suicide. The research also suggests one possible way of addressing lithium non-response. Read more.
The Lancet, June 1, 2024
Team Develops an Innovative, Implantable Ultrasound Device to Stimulate Neurons in Deep-Brain Regions
New Technologies: Deep-Brain Stimulation
- Canan Dağdeviren, Ph.D., Massachusetts Institute of Technology; 2018 BBRF Young Investigator
Researchers developed and tested a tiny, implantable neurostimulation device that uses ultrasound to modify the activity of neurons deep in the brain. The neural stimulator, called ImPULS, could become “a potent neuromodulatory tool” for therapeutic applications ranging from major depression to Alzheimer’s. Read more.
Nature Communications, June 4, 2024
Network Connectivity Patterns in High-Risk Pre-Adolescents Correctly Predicted Depression Symptom Onset 2 Years Later
Diagnostic Tools/Early Intervention: Depression
- Dylan G. Gee, Ph.D., Yale University; 2015 BBRF Young Investigator
Imaging scans from over 1,700 of the 11,000+ children enrolled in the NIMH’s Adolescent Brain Cognitive Development Study (ABCD) revealed connectivity patterns in the scans of healthy 9- and 10-year olds with parental history of depression that predicted the onset of depression symptoms only 2 years later. This addresses the pressing need to identify predictive neural markers for development of depression prior to the onset of adolescence, especially among children at high familial risk. Read more.
Developmental Cognitive Neuroscience, November 27, 2023
Researchers Develop ‘Mood Instability’ Measures to Re-Think How Best to Care for Bipolar Disorder Patients
Diagnostic Tools/Early Intervention; Next-Generation Therapies: Bipolar Disorder
- Sarah H. Sperry, Ph.D., University of Michigan; 2022 BBRF Young Investigator
Evidence based on mood records from 603 bipolar disorder patients collected over 10 years or longer calls into question the assumption in clinical medicine that periods between low and high mood in bipolar disorder are ones of “normal” mood. The team’s finding of considerable “mood instability” between major episodes of depression and mania/hypomania could lead to future efforts to treat such mood fluctuations and in so doing potentially improve quality of life for patients. Read more.
Nature Mental Health, August 8, 2024
Evidence Grows of the Effectiveness of Rapid-Acting Brain Stimulation to Treat Bipolar Depression
Diagnostic Tools/Early Intervention: Depression
- Nolan R. Williams, M.D., Stanford University; 2024 BBRF Colvin Prize; 2019 BBRF Klerman Prize; 2018, 2016 BBRF Young Investigator
- Yvette I. Sheline, M.D., University of Pennsylvania; BBRF Scientific Council; 2005, 2002 BBRF Independent Investigator; 1998 BBRF Young Investigator
Three papers appearing in 2024 (two by Dr. Williams and colleagues; the other by Dr. Sheline’s team) have provided clinical trial-based evidence of the effectiveness and safety of rapid-acting non-invasive brain stimulation therapy to treat people suffering from severe, treatment-resistant bipolar depression. This is of particular importance given the greatly elevated risk of suicide among adults with BD (estimated at 10% - 15% or higher). The three trials involved applications of individually targeted iTBS (intermittent theta- burst stimulation) given 10 times daily in short sessions separated by about 1 hour and continuing over 5 days. The SAINT iTBS-based protocol developed by Dr. Williams‘s team was approved by the FDA for commercialization in treating major depression in 2022. The trials thus far in depressed BD patients have generated similarly high rates of treatment response and remissions. Read more.
Journal of Affective Disorders, August 16, 2024
Brain Stimulation, March 4, 2024
JAMA Psychiatry, July 10, 2024
Network Connectivity Patterns in High-Risk Pre-Adolescents Correctly Predicted Depression Symptom Onset 2 Years Later
Diagnostic Tools/Early Intervention; Next-Generation Therapies: Addiction
- Kevin T. Beier, Ph.D., University of California Irvine School of Medicine; 2017 BBRF Young Investigator
Researchers found that activity of certain neurons in the brain’s globus pallidus can predict behavioral responses to cocaine in mice. This potential biomarker also suggests a possible basis for novel treatment of cocaine and other substance abuse: administration of carnosic acid obtained from rosemary extract. Currently, there are no effective therapeutics for dependence on psychostimulants like cocaine. Read more.
Neuron, August 16, 2024
tDCS Non-Invasive Brain Stimulation Fares Well in Trials for PTSD and Major Depression
Next-Generation Therapies: PTSD, Depression
- Mascha van ’t Wout-Frank, Ph.D., Brown University; 2010 BBRF Young Investigator
- Cynthia H. Y. Fu, M.D., Ph.D., King’s College London, UK; 2006, 2002 BBRF Young Investigator
Two clinical trials co-led by BBRF grantees demonstrate the versatility and potential effectiveness of transcranial direct current stimulation (tDCS), a low-power form of non-invasive brain stimulation, in reducing symptoms of PTSD and major depressive disorder. tDCS uses direct current applied to the scalp to alter neural activity in the cortex and can be used in home- based self-administered applications. The depression study (Dr. Fu and colleagues) was a demonstration of that possibility—users self-administered the treatments over 20 weeks, but were monitored constantly via teleconference. Dr. van ‘t Wout-Frank and colleagues separately reported encouraging results of a double-blinded, randomized, placebo-controlled trial using tDCS to treat U.S. military veterans with warzone-related PTSD. Read more.
Nature Medicine, October 21, 2024
JAMA Psychiatry, March 6, 2024
A Strategy to Sharply Blunt Addictive Reward From Opioids While Retaining Their Pain-Relieving Properties
Basic Research; Next-Generation Therapies: Addiction
- Francis S. Lee, M.D., Ph.D., Weill Cornell Medicine; BBRF Scientific Council; 2010 BBRF Independent Investigator; 2005, 2002 BBRF Young Investigator;
Researchers administered the drug JZL184 in mice to raise levels of 2-AG, a naturally occurring neuromodulator in the endocannabinoid system. This greatly reduced reward from opioids but had no impact on opioids’ pain- relieving properties, suggesting a possible adjunctive therapy to reduce opioid addiction in pain patients. Read more.
Science Advances, November 29, 2024
